Research Of Cardiac Adverse Events And Bleeding Risk In Patients With CYP2C19 Gene Mutation Who Were Treated With Different Doses Of Clopidogrel After PCI

BackgroundIn recent 10 years, as understanding of clopidogrel is more and more mature, the study of clopidogrel resistance also made a lot of progress, there have been many studies that confirm the CYP2C19 gene of coding activation enzyme of clopidogrel metabolism have gene diversity, especially the CYP2C19~2 2~2 3 allele, have largest effect to metabolic of clopidogrel. Doctors gradually realized the importance of mutations CYP2C19 gene in clinical, at the same time, with the development of the biological monitoring technology and the emergence of CYP2C19 gene detection chip, CYP2C19 gene checking become more convenient efficient and low cost. This makes it become a reality to guide patients with coronary artery disease rational using antiplatelet drugs dependent on CYP2C19 genotype. The platelet inhibition rate of patients with CYP2C19 gene mutant was significantly lower than that CYP2C19 gene wild-type when taking conventional doses of clopidogrel. A part of patients during given regular aspirin and clopidogrel dual antiplatelet therapy still appear ischemic events, the phenomenon known as "clopidogrel resistance (CR). In addition, many scholars study found that increasing clopidogrel dosage can improve the effect of clopidogrel antiplatelet, and can reduce the incidence of adverse ischemic events. Some studies have shown that increasing clopidogrel dosage can increase the risk of bleeding, but some scholars holding different views on this issue that increase dosage will not increase the risk of bleeding.ObjectiveTo compare the cardiovascular ischemic events and bleeding risk in patients with CYP2C19~22~23 who were treated with different doses of clopidogrel after PCI.MethodsSelect 339 patients successfully undergoing PCI and accepting CYP2C19 gene test during January 1st 2014 to May 1st 2015 on the first Affiliated Hospital of Zhengzhou University. Including CYP2C19 gene hybrid mutation (CYP2C19~2 1/~2 2 or CYP2C19~2 1/~2 3) 219 cases, random divided into haploid group given 75 mg clopidogrel a day (107 cases), and double group given 150 mg clopidogrel a day (112 cases), CYP2C19 gene wild type given clopidogrel 75 mg a day as the control group (120 cases). All patients were also given aspirin (100mg/day), statin drugs (atorvastatin 20mg/day), after undergoing PCI for 3 days, survey the platelet inhibition ratio (PIR)by thromboelastography. All patients were flowed up in 1 month, 3 months and 6 months after PCI, at the same time survey the platelet inhibition ratio by thromboelastography, record with or without angina attack and attacking frequency, with or without recurrent myocardial infarction, with or without death, whether occurring bleeding events during last follow up (hospital discharge) to this follow up.ResultsADP receptor pathway induced platelet inhibition rate exist significant difference between 3 groups after charging does for 3 days (38.24±19.07%vs 55.27±22.49%vs 59.64±21.58%, P<0.001). Haploid group was obviously low than double group and the control group (P<0.001). Double group and the control group no significant statistical difference(P= 0.202).Patients were followed up for 6 months, recurrent angina rate of three groups respectively was 23.36%,10.71% and 8.33%; recurrent myocardial infarction rate were 8.41%,1.79%,0.83%; and the three group did not occur the digestive tract hemorrhage, cerebral hemorrhage and severe bleeding complications.ConclusionsPatients with CYP2C19 gene hybrid mutation (CYP2C19~2 1/~2 2 or CYP2C19~2 1 /~2 3) and undergoing PCI, can significantly improve the platelet inhibition rate, reduce the incidence of cardiovascular ischemic events, and at the same time, bleeding events were not significantly increased by given double clopidogrel.